The following production processes for D-serine are known:
(i) a process wherein DL-hydroxymethyl hydantoin is converted into N-carbamyl-D-serine with the aid of a microorganism, followed by hydrolysis to obtain D-serine (Japanese Published Unexamined Patent Application No. 61-152291);
(ii) a process wherein a microorganism belonging to the genus Candida, Torulopsis, Cryptococcus, Saccharomycopsis, Hansenula, Escherichia, Klebsiella, Providencia, Microbacteriun, or Serratia and assimilating L-serine but not substantially assimilating D-serine is cultured in a DL-serine-containing medium, and D-serine is isolated from the culture (Japanese Published Unexamined Patent Application No. 64-2594); and
(iii) a process wherein a microorganism having a tyrosinase activity is allowed to act on a reaction solution containing DL-serine and phenol to convert L-serine into L-tyrosine, and remaining D-serine is recovered (Japanese Published Unexamined Patent Application No. 5-91895).
All of these production processes have problems when used as methods for industrially producing D-serine. Specifically, in process (i), the yield of N-carbamyl-D-serine from DL-hydroxymethyl hydantoin is as low as 40%, and a large amount of cells of a microorganism is required as catalyst In process (ii), L-serine remains after the reaction, and this requires the resolution of DL-serine. In process (iii), the substrate concentration is as low as 1%, and harmful phenol is required in the reaction. These problems complicate the industrial application of these production processes.
Eschericia coli is known to have an L-serine deaminase activity for decomposing L-serine into ammonia, pyruvic acid and water [J. Bacteriol., 171, 5095–5102 (1989), Eur. J. Biochem., 212, 777–784 (1993)]. However, it is reported that the enzyme extracted from Escherichia coli needs complex conditions such as the addition of iron and a reducing agent at the time of reaction [J. Bacteriol., 162, 1270–1275 (1985)], and the use of the purified enzyme for D-serine production is not practical.
Escherichia coli is also known to have a D-serine deaminase activity for decomposing D-serine [J. Bacteriol., 121, 1092–1101 (1975)]. Accordingly, D-serine produced using Escherichia coli from DL-serine with the aid of L-serine deaminase is disadvantageously decomposed by the D-serine deaminase, and this sometimes deteriorates the production efficiency.
Thus, a process for efficiently producing D-serine from DL-serine is not yet established in the conventionally known methods.